Molecular Simulations Find Stable Structures in Fragments of Protein G

Tjaša Urbič,1 Tomaž Urbič,2 Franc Avbelj1 and Ken A. Dill3

1National Institute of Chemistry Slovenia, Ljubljana, Slovenia
2Faculty of Chemistry and Chemical Technology, University of Ljubljana, Slovenia
3Department of Pharmaceutical Chemistry, University of California, San Francisco
* Corresponding author: E-mail:

We perform all-atom computer simulations on nearly one hundred 6-, 8-, 10-, and 12-mer peptide fragments of protein G, and look for stable states. We simulated by replica-exchange molecular dynamics using Amber7 with the parm96 force-field and a GB/SA (generalized-Born/solvent accessible) implicit solvent model. We find that useful diagnostics for identifying stable converged structures are the conformational entropy and free energy of each state. A large gap in the ground-state free-energy, and a low entropy indicate convergence to a single preferred peptide conformation. We find that a non-negligible fraction of such structures have some native-like character. Such physics-based modeling may be useful for identifying early nuclei in folding kinetics and for assisting in protein-structure prediction methods that utilize the assembly of peptide fragments.